Wednesday, October 20, 2010

NJ CFS Conference - Update on XMRV by Dr. Mikovitz

Thanks to everyone for letting me let off some steam and rant yesterday (not that you had any choice!). I'm doing better emotionally today and a bit better physically, though I still have crash symptoms (which could also be herx symptoms from a new Lyme treatment - hard to tell). Jamie is still badly crashed, which again is probably both from over-doing and herx reaction from new bartonella treatment. More movies today, but I insisted on a TV-free hour so I could write a bit!!

So, I will attempt to summarize for you the most important points from Sunday's NJ CFS Association Fall Conference. In looking over my notes, I realize that, although all the speakers were good, most of the new information I learned came from the XMRV update from Dr. Judy Mikovitz, the author of the original XMRV study and head researcher at the Whittemore-Peterson Institute, so I'll focus my summary on that. Some of what she presented was in direct response to criticisms presented at last week's CFSAC meeting, so I'm covering the last conference first.

As I mentioned on Monday, Dr. Mikovitz's presentation was extremely technical and she spoke very quickly for over an hour. I have a scientific background, and much of the details she discussed went over my head, so I'm going to focus here on the bottom lines and her conclusions - sorry in advance if I can't explain the details behind these or if I get something a bit mixed up!

XMRV - History

Dr. Mikovitz' father (or maybe step-father) died of prostate cancer, so she devoted her career and life to finding the infectious agent responsible. She's been working in this field for over 20 years. Certain immune system abnormalities in those who were XMRV positive made her wonder if it might also be implicated in ME/CFS.

Dr. Mikovitz also worked on HIV for many years and has a lot of experience with that retrovirus.

Because other known retroviruses, like HIV, tend to mostly affect B and T cells in the immune system, that's where they first looked for XMRV - turns out those are NOT the best places to find XMRV.

The body's antibody response to XMRV is very different from the response to HIV, so you have to look for it in different places within the immune system (WPI found antibodies "against the envelope protein of XMRV" - I didn't entirely understand what this meant but it's important and she emphasized it often).

The first studies to detect XMRV found only sequences or parts of the retrovirus. WPI has since fully sequenced XMRV.

There are two types being found: XMRV and Polytropic MRV (which were found in the more recent FDA/NIH study). Polytropic MRV is also referred to a PMRV.

Although MRV (MLV-Related Retroviruses) have Muerine (i.e. mouse-related) in their name, Dr. Mikovitz emphasized that these retroviruses are not mouse viruses; they are only related to mice (MLV are Muerine Lukemia Viruses) XMRV has ONLY been found in humans, not in mice (this is important in discussions of possible contamination later). Tuft University has studied 75 types of mice, both those bred in labs and those found in the wild, and these retroviruses do NOT exist in mice.

Why is XMRV so hard to find and why are so many CFS/XMRV studies coming back negative?

XMRV is showing great sequence diversity (at first, only sequences or parts of the retrovirus were found) - retroviruses can change, and different sequences or parts are present in different people and in different parts of the body.

Patient selection criteria differs in different studies.

Methods used in different studies so far differ GREATLY.

WPI/Mikovitz first looked in B and T cells and found only partial sequences of XMRV and not very frequently. It is standard procedure to look for retroviruses by looking for their DNA in cells (this method is called PCR).; however, they have found that XMRV is not always detectable this way.

Next, WPI tried looking in plasma and they found more that way - not all studies have used plasma.

How the samples are handled after they're drawn and before they're tested is critically important - it's easy to kill XMRV in the samples if they're improperly stored and handled. Storage and handling have differed greatly in different studies.

WPI has determined that some samples are negative by PCR testing (a method that looks for the DNA of the retrovirus) but are positive using alternate methods. Some studies have ONLY used PCR.

One of the methods commonly employed to find XMRV will only find it 10% of the time.

WPI has found that it is necessary to use multiple methods of detection in each study in order to find all of the XMRV - most negative studies have used only one method.

What About Contamination?

Some people are claiming that the positive XMRV studies in CFS are positive due to contamination of the samples in the laboratory. Dr. Mikovitz addressed this argument.

WPI tested ALL samples for mouse DNA and there was no evidence of contamination (plus, remember that XMRV does not actually exist in mice!).

Both the WPI and the FDA/NIH studies rigorously ruled out contamination with extra testing. ALL of this data was included with the original papers, even though there wasn't room to publish all of the background data.

UK XMRV Study

WPI started a study in March 2010 to look for HMRV (Human MLV-Related Viruses - both X and P) in UK ME/CFS patients.

The study included 50 patients with ME who met the Canadian Consensus Critera, 50% male and 50% female, along with 50 controls. It was a blind study.

The 100 samples were tested blindly by two labs who had never worked with MRV or mice (to ensure there was no possibility of contamination).

The labs first tested plasma and 48% of the ME plasma samples were positive for XMRV (all were also tested for mouse DNA and were negative). Other samples were detectable only after culturing (some sort of special sample preparation). In some samples, only the virus was detectable; on others, only the antibodies were detectable. Multiple testing methods were necessary in order to find all of the XMRV positive samples.

In all, 80% of the ME patients in the study were positive for XMRV.

4% of the controls were also positive for XMRV (in line with the original WPI study).

Dr. Mikovitz emphasized that the XMRV was very difficult to find. They have learned that subtle differences in storage, handling, and testing make a big difference and that multiple methods must be used to find it all.

XMRV Family Studies
(This is the part of the day that totally blew my mind)

In January 2010, WPI did a study using samples from Dr. Cheney's clinic. They tested not only CFS patients but also their families, including children, parents, and siblings.

81% of the Cheney CFS patient samples were positive for XMRV.

Ready for this? 50% of all family members of CFS patients were also positive for XMRV, whether they had any symptoms or not.

They constructed family trees for each family. In addition to people with CFS, they also looked for family members with cancer and autism.

They found XMRV positive: parents with CFS kids; kids with a CFS parent; kids with autism.

In all, 54% of the parents tested were XMRV positive, 59% of the children tested were XMRV positive, and 82% of the kids with autism were XMRV positive.They detected additional XMRV positive people in 16 of 17 families tested who had 1 member with CFS.

Detection of XMRV in these samples required multiple testing methods to find it all.

They have no idea how XMRV might be transmitted between family members.

By the way, the possible link between CFS and autism is not new. Other researchers have suggested it in the past because they see similar immune system dysfunction in kids with autism.

Politics?
(This part is really disturbing to me. I like to believe that people are generally good and do what they believe to be right. I know that's not always the case.)

Are you wondering why we haven't heard about the amazing studies conducted by WPI in the UK and with families from Dr. Cheney's clinic? Dr. Mikovitz says no one will publish them. She said they keep submitting papers to various publications and they keep getting turned down. There has been some confusion on this point in various discussion forums, but this is what Dr. Mikovitz stated during her presentation - that they can't get any of their papers published - I'm assuming that includes these two studies she described.

Dr. Mikovtz said what's happening with XMRV and CFS reminds her very much of the early days of HIV research. She said that just like back then, she has a drawer full of scientific studies no one will publish, but she will just keep on conducting studies and putting them in the drawer until things change.

Dr. Mikovitz also said that some of the people who've been suggesting contamination are people who were involved with the original studies and who saw all of the original data, including those which proved contamination was impossible.

Other speakers also mentioned that politics are involved. The prevailing theory seems to be this: if the CDC confirms that XMRV, a new, dangerous, and transmissible retrovirus, is present in people with CFS (and the CDC has estimated the number of adults in the US with CFS to be 4 million), then they have a huge public health crisis on their hands.

Dr. Mikovitz says that the evidence of XMRV in CFS is actually stronger than the evidence of XMRV in prostate cancer because of the more extensive testing methods used to date.

Rumor is that the National Cancer Institute (NCI) has been told by someone high up in the government to pursue whether XMRV is involved in prostate cancer but should distance themselves from CFS. Though I hate to believe something like this could actually happen, the speaker from NCI at CFSAC last week was the one who suggested that contamination might be responsible for the positive XMRV results in CFS. Dr. Mikovitz said that person has seen all of the data proving contamination is impossible.

OK, I think that covers it. Sorry this turned out to be so long, but I think it is extremely important for all of us to understand. Hope you find this as enlightening as I did.

NOTE: A few kind readers pointed out some errors I made in the above summary after I posted it, so I have corrected them as of 10/21/10. Thank you to those who were kind enough to offer me their assistance.

15 comments:

Thanks, Sue. I hit "print" so fast on this one! I'm getting asked so many questions about CFS in general and XMRV in particular because of my book.

Some of the inquiries are in emails but many come at places I've given book talks. (I've been able to do a few "book talks" if the stores aren't too far from my house and if I accept that I'll feel very sick and be bedbound for a few days afterward- it's worth it though -- people are SO grateful to have someone talking about CFS in public)

I had what I thought was the latest information from a webinar by Dr. Komaroff, but this adds so much new data to what I had.

Wow. I am beginning to really distrust our government when it comes to medical issues that come up ....The truth needs to be told always, and it is not being told with CFS, XMRV, Lyme, etc. etc. etc. On so many levels it is wrong and unethical.The info you shared here was awesome. Thanks. Even wtih my heavy brain fog right now I was able to take it in.

Wow Sue! Thanks you so much for your incredible summary of the conference! I'm still reading/digesting it. BTW, did you know that my brother is Autistic? I have always felt that there was/is a very strong link between the two (CFS/ME & Autism) genetically.

I wonder if anyone has ever done a study on the damage to a country's economy as a result of CFS/ME? There seems to be such a lack of political will to face up to this health crisis, but it seems to me a little investment could go a long way and surely that would be a good thing economically (as well as from a humanitarian point of view - obviously)?

"Other speakers also mentioned that politics are involved. The prevailing theory seems to be this: if the CDC confirms that XMRV, a new, dangerous, and transmissible retrovirus, is present in people with CFS (and the CDC has estimated the number of adults in the US with CFS to be 4 million), then they have a huge public health crisis on their hands."

I really hope Dr. Mikovtz did not mention this because there are far to many ridiculous conspiracy theories circulating around about XMRV. It will also also greatly hurt her reputation among the people she needs to get data published, get funding, and do the large scale researched needed to move XMRV forward.

"Rumor is that the National Cancer Institute (NCI) has been told by someone high up in the government to pursue whether XMRV is involved in prostate cancer but should distance themselves from CFS. Though I hate to believe something like this could actually happen, the speaker from NCI at CFSAC last week was the one who suggested that contamination might be responsible for the positive XMRV results in CFS. Dr. Mikovitz said that person has seen all of the data proving contamination is impossible."

Dr. Mikovtz really should not be saying things like this, this will just make her be looked down upon by other researchers and prospective journals she needs to publish data in. Even begin a CFS patient I am saddened that she is spreading rumors, it makes me loose a lot of respect for her and I donated to WPI and have a positive XMRV test. The truth about XMRV will come out with time, far to many extremely talented and well respected researchers are working on this for them not to get to the bottom of it.

I have had Chronic Fatigue Syndrome (CFS or CFIDS) since March 2002. My 19-year old and 16-year old sons also have CFS, and my older son also has Lyme disease plus two other tick infections. This blog is about how our family is learning to live with chronic illness, with a focus on living and enjoying our lives in spite of these challenges.